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Updated: Jul 6, 2026
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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Glucocorticoid resistance in humans.
1The Departments of Surgery and Medicine, Surgical Research Center, University of Connecticut Health Center, Farmington, CT 06030-1110, USA.
Trends in Endocrinology and Metabolism: TEM
|April 1, 1995
Summary
Generalized inherited glucocorticoid resistance, a rare disorder from glucocorticoid receptor mutations, presents with hypercortisolism but balanced resistance, avoiding adrenal insufficiency or Cushingoid features. Clinical signs improve with dexamethasone therapy.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Generalized inherited glucocorticoid resistance is a rare genetic disorder.
- It stems from mutations in the glucocorticoid receptor gene.
- The condition is clinically defined by hypercortisolism.
Purpose of the Study:
- To describe the clinical and molecular characteristics of generalized inherited glucocorticoid resistance.
- To elucidate the balanced pituitary and peripheral resistance mechanism.
- To highlight the therapeutic response to dexamethasone.
Main Methods:
- Clinical case description and analysis.
- Genetic analysis of glucocorticoid receptor mutations.
- Hormonal level assessment (ACTH, cortisol, androgens, mineralocorticoids).
Main Results:
- Patients exhibit hypercortisolism due to ACTH excess stimulating the adrenal gland.
- Despite high cortisol, adrenal insufficiency and Cushingoid features are absent due to balanced resistance.
- Clinical manifestations, including excess adrenal androgens and mineralocorticoids, respond to dexamethasone treatment.
Conclusions:
- Generalized inherited glucocorticoid resistance is characterized by a unique balance between pituitary and peripheral resistance.
- The condition results in specific clinical features related to adrenal androgen and mineralocorticoid overproduction.
- Dexamethasone is an effective treatment for the clinical manifestations of this disorder.
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